Overview

Hormonal (really anti-hormonal) therapies for breast cancer change the balance of estrogen in the body. The effect of these treatments is to block hormones that can stimulate growth of breast cancer cells in breast cancers with hormone receptors. Hormonal therapies can prevent cancer from coming back (recurrence) in early breast cancer or control disease in advanced breast cancer.

When a breast cancer is removed or a biopsy is done, one of the tests in the laboratory determines whether or not there are estrogen and/or progesterone receptors on your breast cancer cells. These receptors are like "docking stations" that the hormones estrogen and progesterone can connect to and stimulate the growth of breast cancer. When the receptors are present, the breast cancer is estrogen receptor positive (ER+) and /or progesterone receptor positive (PR+). If the breast cancer cells have estrogen and/or progesterone receptors, this predicts that the hormonal therapies will be a useful part of your treatment. If your breast cancer cells have few or no estrogen or progesterone receptors (ER-negative, PR-negative) it is unlikely that the anti-estrogen therapies will benefit you.

If either of the hormone receptors is positive (ER+ or PR+), then the hormone therapies are used as a treatment for early stage breast cancer. Large clinical trials have shown that hormone therapies can prevent recurrence and death from breast cancer. Hormone therapies can also be used to treat a recurrence in the breast and lymph nodes or to treat advanced or metastatic breast cancer (outside the breast in other organs such as the bone).

If you are pre-menopausal (still having periods, menstruating) most of your estrogen is made in your ovaries. If you are post-menopausal (no menstrual periods for a year, often confirmed by blood tests) you still produce small amounts of estrogen in your body - just not in the ovary. The adrenal glands (near your kidneys) produce a hormone, androstenedione (a weak male hormone) that is then changed into estrogen by an enzyme called aromatase. The aromatase enzyme is found in many cells including fat and muscle. Therefore, whether you are pre or post menopausal will effect your treatment options for hormone therapy. Blocking estrogen stimulation of hormone receptor positive breast cancer is the goal in both pre- and post-menopausal women, but the treatment strategies may be different.

Hormonal Therapy in Early Breast Cancer

The use of anti-hormone medications in early stage breast cancer is called adjuvant therapy (or treatment given after surgery or surgery and radiation to decrease the risk of cancer recurrence). It may be the only systemic (system-wide) treatment or it may also be given following chemotherapy. The recommendations that you will hear from your physician(s) take many factors into consideration including: your overall health, your menopausal status, estrogen and progesterone receptors, another receptor called HER2/neu, the stage (how far along the cancer is), the grade (a measure of tumor biology and behavior) and other tests that are done to predict risk. Hormone therapy is usually given for 5 years; some studies are looking at longer term treatment in higher risk cancers.

Once you know that your breast cancer is ER positive and/or PR positive, the issues that you and your physician(s) will consider include:

What is the risk of my breast cancer coming back (recurrence) if I do local therapy (surgery, radiation) alone?

How much can hormonal therapy lower my risk of the cancer coming back? (recurrence can be in the breast or in other organs)

What is/are the best hormone therapy medications for me?

What are the risks and side effects of those medicines?

Does the benefit outweigh the risk?

Their recommendations and your preferences can then lead to a treatment decision.

Treatment Options

One treatment option is to block the action of estrogen by blocking the receptors on the breast cancer cells:

SERMS(selective strogen receptor modulators) block the receptors (loading docks) so that the growth signals to the cells are interrupted. Tamoxifen (Nolvadex®) is a SERM and is the standard of care for pre-menopausal women. Tamoxifen works in a setting where estrogen is still being produced by the ovaries as well as in post-menopausal women. Tamoxifen reduces the risk of recurrence and death from hormone receptor positive breast cancer; studies have shown that 5 years of treatment still reduces risk at 15 years after diagnosis.

Tamoxifen is a complex medication that has anti-estrogen effects on some tissues and estrogen-like effects on other tissues. The anti-estrogen effects lead to the primary benefit of reducing breast cancer recurrence risk and the menopausal side effects like hot flashes and vaginal dryness. The estrogen-like effects lead to an added benefit of maintaining bone strength and side effects of an increased risk of blood clots and a small increased risk of developing uterine cancer. Read more about tamoxifen (Nolvadex®) in the Specific Drug Information section below, and on the National Cancer Institute's FactSheet on tamoxifen.

In some settings, pre-menopausal women may receive injections of goserelin (Zoladex®), leuprolide (Lupron®), or triptorelin (Trelstar®) which are drugs that stop hormones from the pituitary gland in the brain from stimulating the production of estrogen in the ovaries. This treatment, called ovarian suppression, is usually done along with treatment with tamoxifen. Clinical trials are evaluating treatment with ovarian suppression combined with aromatase inhibitors for pre-menopausal women. Ovaries can be surgically removed or radiated to block estrogen, but this is not often done (except for preventative surgery in cases where the risk of ovarian cancer is high).

Another option is to lower the level of hormones in the body that can stimulate breast cancer cell growth. Estrogen stimulates breast cancer growth. If the amount of estrogen is decreased, breast cancer growth is decreased.

Aromatase inhibitors lower the amount of estrogen made outside the ovaries.

Aromatase inhibitors only work in post-menopausal women because they do not block estrogen from the ovaries. Examples of aromatase inhibitors include: anastrozole (Arimidex®), letrozole (Femara®) and exemestane (Aromasin®). These drugs can be given instead of tamoxifen or after 2 or 3 years of tamoxifen as adjuvant hormone therapy for early stage breast cancer. All are pills taken by mouth on a daily basis.

Hormonal Treatment of Advanced or Metastatic Breast Cancer

Hormonal therapy can be effective in controlling advanced breast cancer in women who have ER+ and /or PR+ disease. The breast cancer will sometimes be retested (by biopsy or surgery) for receptor status because it may change from that of the original breast cancer (usually going from positive to negative), or the original test might have been incorrect.

Treatment choices are similar to those reviewed above for early stage breast cancer, and include tamoxifen (Nolvadex®) or a similar drug called toremifene (Fareston®) and the aromatase inhibitors - anastrozole (Arimidex®), letrozole (Femara®) and exemestane (Aromasin®).

Again menopausal status affects the choice of therapy. For pre-menopausal women, ovarian suppression is usually used along with either tamoxifen or aromatase inhibitors. In post-menopausal women, the aromatase inhibitors (AI's) have been shown to be more effective than tamoxifen and are a very good treatment strategy. Tamoxifen may still be effective and is often used after the aromatase inhibitors stop working.

Treatment for advanced breast cancer includes a series of medications used to control the cancer. Typically one medication is given until the cancer is no longer responding, then a switch is made to another effective medication. Additional options for hormone therapy are described below.

There is another drug that is only used to treat advanced breast cancer at this time. Fulvestrant (Faslodex®) is a "pure" estrogen receptor blocker that works like tamoxifen to block the receptors in the breast cancer cells. Unlike the other hormonal therapies described above which are oral medicines, fulvestrant is an injection given into the muscle once per month. Fulvestrant can be used either before or after aromatase inhibitor therapy.

Megestrol acetate (Megace®), acts in a similar way to the hormone progesterone, and is also an effective treatment for advanced breast cancer. Megace® is given either as a pill or a liquid and can also improve appetite in people with poor appetites due to cancer.

Other hormonal therapies are under study, including the use of high dose estrogens. Estrogen can cause blood clots, so this medication must be used with caution and is usually given after the above medications are no longer working to control the cancer.

Clinical Trials

You may be eligible for treatment on a clinical trial using hormone therapy. There are ongoing clinical trials that will continue to provide information that will help you and your physician(s) tailor your treatment decisions. New hormonal agents are being studied, new trials will open and this area of therapy, for women with estrogen and/or progesterone positive breast cancer, will expand. To find these trials, visit the UCSF Comprehensive Cancer Center's Clinical Trials page or the NCI affiliated matching program breastcancertrials.org.

Specific information on individual drugs

Please see below for specific information on each drug. To report side effects, remember that you may contact the Breast Care Center at 415-353-7070; the Call Center staff will take your call. During clinic hours Monday through Friday, the triage nurse will return your call. After 5 p.m. or on weekends, an on-call doctor will return your call.

Anastrozole (Arimidex®)

How does this drug work?

Arimidex® is a hormonal drug that prevents the growth of breast cancer by inhibiting the enzyme aromatase, which is involved in the production of estrogen. Femara® significantly lowers the amount of estrogen in post-menopausal women by inhibiting the conversion of androgens (made in the adrenal glands) to estrogen. It is taken orally in a 1-mg dose daily. It is currently indicated for postmenopausal women with advanced breast cancer. It should not be take by premenopausal women after progression or prior treatment with tamoxifen.

Common side effects

Arimidex® is usually well tolerated. Less common side effects with your type of chemotherapy:

Nausea, vomiting, and diarrhea

Headache, back pain

Hot flashes

Tingling or swelling of hands and feet

Difficulty breathing

Skin rash

Mental depression

Dizziness

Chest pain

Usual Dosing

You should take 1 tablet (1 mg) by mouth daily. It may be taken with or without food at any time of the day.As with any drug, other side effects that were not mentioned may occur.

General concerns

Report to your doctor any side effect you may experience.

Report any symptoms which are unusual for you.

If you have a fever of 101°F (38.3°C) with or without chills, or chills alone, call the nurse immediately. If you cannot reach the nurse or on-call doctor (after hours), go to an emergency room.

Other concerns with Arimidex®

Continue taking this drug even if you feel ill. Most side effects will go away with time (2-6 weeks) as your body adjusts to the medicine. However, report any side effects to your doctor.

Exemestane (Aromasin®)

How does this drug work?

Aromasin® is a hormonal drug that prevents the growth of breast cancer by inhibiting the enzyme aromatase, which is involved in the production of estrogen. Aromasin® significantly lowers the amount of estrogen in post-menopausal women by inhibiting the conversion of androgens (made in the adrenal glands) to estrogen. It is taken orally in a 25-mg dose daily after a meal. It is currently indicated for postmenopausal women with advanced breast cancer after progression or prior treatment with tamoxifen. It should not be taken by premenopausal women.

General Side Effects

Aromasin® is generally well tolerated and adverse effects are usually mild to moderate. Only about 3% of women would be expected to discontinue Aromasin® due to side effects. Late discontinuation of therapy (after 3 months) is uncommon.

Less common side effects with your type of chemotherapy

As with any drug, other side effects that were not mentioned may occur

General concerns

Report vomiting or nausea that is not relieved with anti-nausea medication.

Immediately report any fevers of 101° F or higher, with or without chills.

Report nose bleeds, gum bleeds, or any unusual bruising.

Ask your doctor about a birth control method for you.

Report any symptoms that are unusual for you.

Report any swelling which is uncomfortable.

Report any shortness of breath.

Letrozole (Femara®)

How does this drug work?

Femara®is a hormonal drug that prevents the growth of breast cancer by inhibiting the enzyme aromatase, which is involved in the production of estrogen. Femara® significantly lowers the amount of estrogen in post-menopausal women by inhibiting the conversion of androgens (made in the adrenal glands) to estrogen. It is taken orally in a 2.5-mg dose daily after a meal. It is currently indicated for postmenopausal women with advanced breast cancer. It should not be take by premenopausal women after progression or prior treatment with tamoxifen.

General Side Effects

Femara® (letrozole tablets) was generally well tolerated in two controlled clinical trials. Only about 3% of patients discontinued Femara®.

Less common side effects with your type of chemotherapy

As with any drug, other side effects that were not mentioned may occur

General concerns

Report vomiting or nausea that is not relieved with anti-nausea medication.

If you have a fever of 101° F (38.3° C) with or without chills, or chills alone, call the nurse immediately. If you cannot reach the nurse or on-call doctor (after hours), go to an emergency room.

Report nose bleeds, gum bleeds, or any unusual bruising.

Ask your doctor about a birth control method for you.

Report any symptoms that are unusual for you.

Report any swelling which is uncomfortable.

Report any shortness of breath.

Megestrol acetate (Megace®)

How does this drug work?

Megace® is a progesterone-like drug which prevents the activity of hormones that can cause breast cancer to grow.

Common side effects

Swelling of the hands and feet

Weight gain

Increased appetite

Vaginal bleeding or missed period

Less common side effects with your type of chemotherapy

Skin rash

Blood clots and inflammation of a vein (phlebitis)

Mental depression, mood changes

Usual Dosing

The usual dose is 40-mg orally four times a day and may be taken with or without food.

As with any drug, other side effects that were not mentioned may occur

General concerns

Oral contraceptives (the "pill") are not recommended for women with breast cancer. Ask your doctor about a birth control method for you.

If you become pregnant, tell your doctor or nurse immediately

If you are planning to become pregnant, consult with your doctor first.

Report to your doctor any side effect you may experience.

Report any symptoms which are unusual for you.

Tamoxifen (Nolvadex®)

How does this drug work?

Tamoxifen is a drug that blocks the activity of estrogen hormones that can cause breast cancer to grow.

CYP2D6 Testing

CYP2D6 is a liver enzyme that metabolizes tamoxifen into its active drug form. Seven percent of Caucasian women and 3% of women of other ethnicities may have a deficiency in the CYP2D6 enzyme. Women who have a deficiency in CYP2D6 may have less benefit from taking tamoxifen. CYP2D6 gene testing can determine if your CYP2D6 status. The test involves a simple blood test to collect some cells to do the DNA test. Talk with your health care provider about this test if you are taking tamoxifen or if you are thinking about taking tamoxifen.

Antidepressants and Other Medications

Some antidepressants, such as fluoxetine (Prozac®) and paroxetine (Paxil®), can decrease the effectiveness of Tamoxifen. Other antidepressants, such as venlafaxine (Effexor®), do not decrease the effectiveness of Tamoxifen. If you are taking an antidepressant, talk with you health care provider to check if there is an interaction between your medications.

There are various other medications that may alter the effectiveness of tamoxifen. Make sure you tell your health care provider all medications you are currently taking before you start tamoxifen therapy.

Common side effects

Tamoxifen is usually well tolerated

Hot flashes

Less common side effects with your type of hormone therapy

Weight gain

Vaginal discharge, dryness, or bleeding

Blood clots and inflammation of a vein (phlebitis)

Skin rash

Swelling of the hands and feet

Mental depression, mood changes

An increased risk of uterine cancer to about one in 500 to 700 cases per year is estimated. The uterine cancers that have occurred have been at an early stage and are thought to be curable in most cases.

Difficulty sleeping

Very rare complications include

Eye problems that include retinal changes

Liver cancer: two reports in women taking more than 40 milligrams of tamoxifen per day

As with any drug, other side effects that were not mentioned may occur.

Usual Dosing

Tamoxifen dose is 20 mg daily and may either be taken 2 times per day (10 mg tablets) or 1 time per day (20 mg tablets). If changes are made to the usual dosing schedule, your physician or nurse will explain those changes.

Tamoxifen may be taken with or without food.

Oral contraceptives (the "pill") or any form of estrogen replacement are not recommended for women with breast cancer. Ask your doctor about an acceptable birth control method or estrogen compound for you.

If you become pregnant, tell your doctor or nurse immediately.

If you are planning to become pregnant, consult with your doctor first.